Data for:Targeted myocardial ablation mediated by focused ultrasound and thermo-responsive suicide gene therapy: a proof-of-concept investigation

Myocardial volume reduction therapy (MVRT) is a cornerstone intervention for obstructive hypertrophic cardiomyopathy (HCM), yet all currently available MVRT techniques are invasive. In this study, we introduced an innovative myocardial reduction strategy utilizing low-intensity continuous focused ultrasound (FUS). This method integrates spatially targeted FUS-induced hyperthermia with a heat-inducible suicide gene system, specifically inducible caspase-9 (iCas9), driven by the HSP70 promoter. The approach is theoretically designed to achieve myocardial tissue ablation under hyperthermic conditions. However, initial evaluations indicated that the wild-type HSP70 promoter demonstrated insufficient thermal responsiveness, thereby significantly diminishing the effectiveness of the iCas9 system. Through rational dissection and recombination of the promoter sequence, a modified HSP70 promoter with significantly enhanced thermal responsiveness was ultimately engineered. The optimized HSP70-iCas9 system, driven by the engineered HSP70 promoter, was subsequently integrated with a customized FUS heating platform, resulting in the successful induction of controlled apoptosis in murine cardiomyocytes under mild hyperthermia conditions.